Isoflavones have been extensively described in the scientific and patent literature as possessing a range of biological activities including oestrogenic and anti-cancer effects.
Naturally occurring isoflavones are found in plants such as legumes. These include soy, chick peas, lentils, beans (broad, haricot, kidney, lima, navy, etc), grams (Bengal, horse and green) and clovers. Soy and clover contain the highest levels of isoflavones.
Principal oestrogenic and anti-cancer isoflavones are genistein, daidzein, formononetin, and biochanin. In plants these compounds occur principally in the glycoside form bound to sugars such as glucose. The formulae of these isoflavones are as follows: ##STR1## the structure of biochanin is the same as for genistein but with a 4'-methoxy group, and similarly formononetin has the same structure as daidzein, but with a 4'-methoxy group. Isoflavone-containing plant extracts, such as from soy, arc commercially available in some countries particularly as health supplements. Such extracts are specifically prepared for their isoflavone content, considerable effort being made to ensure the extracts contain maximum isoflavone content, the isoflavones being regarded as the biologically active species.
International Patent Application No. PCT/AU93/00230, incorporated herein by reference, describes isoflavone-containing extracts of a plant, such as legumes and clovers, and therapeutic uses for such isoflavone-containing extracts. The isoflavone extracts described therein specifically contain genistein, daidzein, formononetin and biochanin.
A recent clinical finding described in the Medical Journal of Australia (Stephens, F. O.. (1997) M. J. A., 167, 138-140) showed that an isoflavone extract prepared according to PCT/AU93/00230 produced major degenerative changes (including apoptosis) as shown by a prostatectomy specimen surgically removed from a patient with moderately high-grade adenocarcinoma. The patient received oral administration of the isoflavone-containing extract at a daily dose of 160 mg for seven days prior to surgery. The prostatectomy specimen showed a moderately high-grade adenocarcinoma with patchy microvaculation and prominent apoptosis, while no change was seen in normal prostate cells. The degenerative changes in the prostatectomy specimen, especially the apoptosis, were indicative of androgen deprivation and typical of a response to oestrogen therapy. This finding provided direct support for the oestrogen-like activity of the isoflavones genistein, daidzein, formononetin and biochanin exerting a positive therapeutic treatment in prostate cancer.
The inventors have surprisingly found that extracts of isoflavone-containing plants, such as soy or clover from which genistein, daidzein, formononetin and biochanin have been removed, have significant anti-cancer activity. This finding was contrary to all predictions, specifically given the absence of genistein, daidzein, formononetin and biochanin, regarded as the active anti-cancer agents.